Our findings suggest that mutation of PTCH1 is correlated with early recurrence of breast cancer patients and will become a powerful predictor for recurrence of breast cancer.
Bmi1 was downregulated using two approaches in the mouse breast cancer stem cell line FMMC 419II-a small molecule inhibitor (PTC 209) and stable transfection with a Bmi1 shRNA plasmid.
Furthermore, inhibition of expression of miR-200c or miR-141 overcomes tumor suppressive effects of PTC-209 including induction of cellular senescence and downregulation of breast cancer stem cell phenotype.
Differential association of alterations in FANCC and PTCH1 with that of PHF2, XPA and two breast cancer susceptibility genes (BRCA1/BRCA2) in the two age groups suggests differences in their molecular pathogenesis and dysregulation of multiple DNA repair pathways as well as hedgehog dependent stem cell renewal pathway.
In human clinical samples, altered hedgehog signaling occurs early in breast cancer development, with PTCH1 expression reduced in approximately 50% of ductal carcinoma in situ (DCIS) and invasive breast cancers (IBC).
GLI1 protein and mRNA, and PTCH1 and sonic hedgehog (SHH) proteins were elevated in 3 of 10 breast cancers; however, PTCH1 transcripts were not consistently increased.
However, the biallelic Pro1315Leu (C3944T) polymorphism of PTCH1 was significantly associated with breast cancer in 41 Bavarian patients compared to 85 healthy controls.